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Brain structure in autism: a voxel-based morphometry analysis of the Autism Brain Imaging Database Exchange (ABIDE)

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Abstract

Increased brain volume is a consistent finding in young children with autism spectrum disorders (ASD); however, the regional specificity and developmental course of abnormal brain structure are less clear. Small sample sizes, particularly among voxel-based morphometry (VBM) investigations, likely contribute to this difficulty. Recently established large-scale neuroimaging data repositories have helped clarify the neuroanatomy of neuropsychiatric disorders such as schizophrenia and may prove useful in ASD. Structural brain images from the Autism Brain Imaging Database Exchange (ABIDE), which contains over 1100 participants, were analyzing using DARTEL VBM to investigate total brain and tissue volumes, and regional brain structure abnormalities in ASD. Two, overlapping cohorts were analyzed; an ‘All Subjects’ cohort (n = 833) that included all individuals with usable MRI data, and a ‘Matched Samples’ cohort (n = 600) comprised of ASD and TD individuals matched, within each site, on age and sex. Total brain and grey matter volumes were enlarged by approximately 1–2 % in ASD; however, the effect reached statistical significance in only the All Subjects cohort. Within the All Subjects cohort, VBM analysis revealed enlargement of the left anterior superior temporal gyrus in ASD. No significant regional changes were detected in the Matched Samples cohort. There was a non-significant reduction in the correlation between IQ and TBV in ASD compared to TD. Brain structure abnormalities in ASD individuals age 6 and older consists of a subtle increase in total brain volume due to enlargement of grey matter with little evidence of regionally specific effects.

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    Authors and Affiliations

    1. Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA

      Kaitlin Riddle, Carissa J. Cascio & Neil D. Woodward

    2. Center for Cognitive Medicine & Psychotic Disorders Program, Vanderbilt Psychiatric Hospital, Suite 3057, 1601 23rd Ave. S., Nashville, TN, 37212, USA

      Neil D. Woodward

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    1. Kaitlin Riddle
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    2. Carissa J. Cascio
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    Correspondence to Neil D. Woodward.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the original data sources on which this study is based.

    Funding

    This research was supported by funding from NIMH R21MH101321 (C.J.C. & N.D.W.) and the Jack Martin, MD., Research Professorship in Psychopharmacology (held by N.D.W.).

    Additional information

    Kaitlin Riddle and Neil D. Woodward contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    ESM 1

    Example raw T1 scan quality and segmentation results for three subjects (S1, S2, S3) included in the ABIDE. Raw T1 scans for S1 and S2 were considered usable; however, segmentation failed for S2 (note the extensive misclassification of grey matter as CSF in medial and lateral frontal cortex indicated with white arrows on axial slice). The raw T1 scan for S3 is an example of a scan considered unusable. (DOCX 2276 kb)

    ESM 2

    Mean and standard deviation of total brain and tissue volumes by site in autism spectrum disorder (ASD) and typical development (TD) for the All Subjects cohort (n = 833). Abbreviations: TBV = Total Brain Volume; CSF = Cerebrospinal Fluid. * Significant difference between groups (p ≤ .05) based on independent groups t-test. (DOCX 120 kb)

    ESM 3

    Mean and standard deviation of total brain and tissue volumes by site in autism spectrum disorder (ASD) and typical development (TD) for the Matched Samples cohort (n = 600). Abbreviations: TBV = Total Brain Volume; CSF = Cerebrospinal Fluid. * Significant difference between groups (p ≤ .05) based on independent groups t-test. (DOCX 124 kb)

    ESM 4

    Grey matter volume increase in ASD compared to TD with and without covarying for IQ. The same region in the left anterior superior temporal gyrus exhibited relatively greater grey matter volume in ASD regardless of whether or not IQ was included as a covariate in the analysis. (DOCX 706 kb)

    ESM 5

    Bivariate correlations between total brain volume (TBV) and IQ in autism spectrum disorder (ASD) and typical development (TD) for the All Subjects and Matched Samples Cohorts. Within the All Subjects cohort, the correlation between TBV and IQ in ASD r = .16 (p = .002) for the ASD group (n = 381) and r = .23 (p < .001) in the TD group (n = 430). Within the Matched Samples cohort, the correlation between TBV and IQ in ASD (n = 297) was r = .20 (p = .001) and r = .25 (p = <.001) in the TD group (n = 293). Results differ slightly from the partial correlations reported in text which covaried for age, sex, and site (bivariate correlations are reported and displayed here for clarity). (DOCX 173 kb)

    ESM 6

    Demographic for each age band within the All Subjects Matched Samples cohorts (DOCX 20 kb)

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    Riddle, K., Cascio, C.J. & Woodward, N.D. Brain structure in autism: a voxel-based morphometry analysis of the Autism Brain Imaging Database Exchange (ABIDE). Brain Imaging and Behavior 11, 541–551 (2017). https://doi.org/10.1007/s11682-016-9534-5

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